Turner syndrome

Definition

Turner syndrome is a birth defect caused by the absence of an X chromosome in some or all cells of a female, which inhibits sexual development and usually causes infertility.

Description

Chromosomes are structures in the nucleus of every cell in the human body that contain the genetic information necessary to direct the growth and normal functioning of all cells and systems of the body. A normal individual has a total of 46 chromosomes in each cell, two of which are responsible for determining gender. Normally, females have two X chromosomes, and males have one X and one Y chromosome.

In Turner syndrome, an error occurring very early in development results in an abnormal number and arrangement of chromosomes. Most commonly, an individual with Turner syndrome will be born with 45 chromosomes in each cell rather than 46. The missing chromosome is an X chromosome. The affected person is always female.

Turner syndrome may result in a wide spectrum of symptoms, from major heart defects to minor cosmetic issues. Some individuals with Turner syndrome may only have a few symptoms while others may have many. Almost all girls with Turner syndrome have short stature and loss of ovarian function, but the severity of the symptoms varies among individuals.

Turner syndrome is also referred to as Bonnevie-Ullrich syndrome, gonadal dysgenesis, and monosomy X.

Demographics

The prevalence of Turner syndrome is widely reported as being approximately one per 2,500 live female births, although researchers have reported prevalence rates that range from one in 3,125 to one in 5,000 live female births. About 1 to 2 percent of all female conceptions have a missing X chromosome. Of these, the majority (99%) spontaneously abort, usually during the first trimester of pregnancy.

Causes and symptoms

Turner syndrome usually occurs sporadically, which means that the mutation occurs during fetal development and is not inherited from either parent. In rare cases, a parent may carry rearranged chromosomes that can result in Turner syndrome in a daughter, which is the only situation in which the Turner syndrome is inherited.

More than half of all girls with Turner syndrome are mosaics, which means that the mutation occurs in some but not all cells of their body. Therefore, Turner syndrome can vary in severity. The fewer the affected cells, the milder the disease.

Symptoms of a girl with Turner syndrome include:

• short stature
• webbed skin of the neck
• abnormal eye features (drooping eyelids)
• abnormal bone development, such as a "shield-shaped," broad flat chest
• absent or retarded development of secondary sexual characteristics that normally appear at puberty , including sparse pubic hair and small breasts
• coarctation (narrowing) of the aorta
• bicuspid aortic valve
• infertility
• dry eyes
• absence of menstruation

Growth in children with Turner syndrome is characterized by a slight intrauterine growth retardation , relatively normal growth rates for the first several years of life, a progressive deceleration of growth later in childhood, and the lack of a pubertal growth spurt. The average height of Turner women is 147 cm (57.8 inches), varying between 135 (53 inches) and 163 cm (64 inches). This is about 20 cm (7.8 inches) shorter than the height of women with normal chromosomes.

Normal pubertal development and spontaneous menstrual periods do not occur in the majority of children with Turner syndrome. Most girls with Turner syndrome do not have ovaries with healthy oocytes capable of fertilization and embryo formation. However, it is estimated that 3 to 8 percent of girls with a single X chromosome and 12 to 21 percent of females with sex chromosome mosaicism may have normal pubertal development and spontaneous menstrual periods. A few pregnancies have been reported in women with Turner syndrome.

Individuals with Turner syndrome report an increased incidence of fractures in childhood and osteoporotic fractures in adulthood. The primary cause of osteoporosis may be inadequate levels of estrogen circulating in the body; however, defects in bone structure or strength may also be related to the loss of unknown X-chromosome genes.

The incidence of type II diabetes, also known as insulin resistant diabetes (glucose intolerance), has been reported to be increased in Turner syndrome, with individuals having twice the risk of the general population for developing this disease. The muscles of many persons with Turner syndrome fail to use glucose efficiently, which may contribute to the development of high blood sugar.

Many women with Turner syndrome have high blood pressure, which may even occur during childhood. High blood pressure may be due to aortic constriction or to kidney abnormalities; however, in a majority of cases, no specific cause for high blood pressure can be identified.

Kidney problems are present in about one third of girls with Turner syndrome and may contribute to high blood pressure. Three types of kidney problems have been reported: the presence of a single horse-shoe shaped kidney (normally two distinct, bean-shaped structures are present); an abnormal urine-collecting system; or an abnormal artery supply to the kidneys.

From 5 to 10 percent of girls with Turner syndrome have a severe constriction of the major blood vessel coming from the heart (coarctation of the aorta ). This defect is thought to be a result of an obstructed lymphatic system compressing the aorta during fetal development. Other major defects and its major vessels are reported to a lesser degree. As many as 15 percent of children with Turner syndrome have bicuspid aortic valves, where the major blood vessel from the heart has only two rather than three components to the valve regulating blood flow.

Juvenile rheumatoid arthritis, an autoimmune condition, has been associated with Turner syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. Girls with Turner syndrome have an elevated prevalence rate of dental caries and such other periodontal conditions as gum disease and plaque.

Approximately one-third of girls with Turner syndrome have a thyroid disorder, usually hypothyroidism . Symptoms of this condition include decreased energy, dry skin, cold-intolerance, and poor growth.

Contrary to earlier reports, most individuals with Turner syndrome are not mentally retarded. They may have some learning disabilities, particularly with regard to spatial perception, visual-motor coordination, and mathematics. This specific learning problem is referred to as Turner neurocognitive phenotype and appears to be due to loss of X chromosome genes important for selected aspects of nervous system development. The verbal skills of girls with Turner syndrome are usually normal. Some girls with Turner syndrome may also have difficulties with memory and motor coordination, which may be related to estrogen deficiency.

When to call the doctor

Parents should call their healthcare provider if their infant has symptoms of this disorder or if an adolescent girl's sexual development appears to be delayed.

Diagnosis

Turner syndrome is either diagnosed at birth because of associated anomalies or at puberty when there is absent or delayed menses and delayed development of normal secondary sexual characteristics. During a physical examination, the doctor looks for underdeveloped breasts and genitalia, webbed neck, short stature, low hairline in back, simian crease (a single crease in the palm), and abnormal development of the chest. An ultrasound may reveal small or undeveloped female reproductive organs while a gynecologic examination may reveal a dry vaginal lining. A kidney ultrasound can be used to evaluate abnormalities of the kidneys. After diagnosis, echocardiogram (heart ultrasound) and an MRI of the chest are performed to evaluate possible cardiac defects.

Hands and feet of infants with Turner syndrome may be swollen or puffy at birth; there may be swelling at the nape of the neck. These babies often have soft nails that turn upwards on the ends when they are older. These features appear to be due to obstruction of the lymphatic system during fetal development. Another characteristic cosmetic feature is the presence of multiple pigmented nevi (colored spots on the skin).

Turner syndrome is confirmed on the basis of genetic analysis of chromosomes, which can be done prior to birth. However, the predictive value of amniocentesis in diagnosing Turner syndrome varies from 21 to 67 percent. There is no significant relation between the mother's age and risk of Turner syndrome.

Treatment

Most individuals with Turner syndrome require female hormone therapy to promote development of secondary sexual characteristics and menstruation. The time of beginning therapy varies with individuals. Experts recommend that therapy begin when a woman expresses concern about her onset of puberty or by the age of 15. Girls and women with Turner syndrome should be treated with estrogen/progesterone to maintain their secondary sexual development and to protect their bones from osteoporosis until at the least the usual age of menopause (50 years). The use of estrogen therapy may also improve memory and motor coordination problems associated with estrogen deficiency. Assisted reproductive technology may allow for women with Turner syndrome to become pregnant with donated ooctyes.

All women receiving long-term, female hormone therapy require periodic gynecological examinations, because those with Turner syndrome have an increased risk of developing neoplasms, such as gonadoblastoma and dysgerminoma, which arise from their rudimentary streak gonads (a condition in which germ cells are absent and the ovary is replaced by a fibrous streak).

Because it is so dangerous, experts suggest early screening and surgery for aortic coarctation of the artery in girls with Turner syndrome. Bicuspid aortic valves can deteriorate or become infected, so it is advised that all girls with Turner syndrome undergo annual cardiac evaluations. Kidney problems may also be corrected surgically, but there still may be a tendency for high blood pressure and infections. Diabetes type II can be controlled through careful monitoring of blood-sugar levels, diet, exercise , regular health care, and medication if necessary. Hypothryoidism can be easily treated with thyroid hormone supplements.

Plastic surgery to correct webbing of the neck should be considered at an early age (before entering school) for girls with Turner syndrome.

Final adult height in individuals with Turner syndrome can be increased if growth hormone (GH) treatment is given relatively early in childhood. However, not all individuals get a good growth response to GH.

Prognosis

Most children with Turner syndrome can live relatively normal lives. The prognosis for a person with Turner syndrome is dependent on the other associated conditions that may be present. Care must be taken to regularly monitor patients for the health problems that are associated with Turner syndrome. For example, heart or kidney defects may significantly impact their quality of life. Without these types of conditions, however, their life expectancy is normal. Support will be necessary to help an adolescent girl cope with body image issues and to help some women accept the fact that they will never be able to have children.

Parental concerns

Families may wish to seek counseling regarding the effects of the syndrome on relationships within thefamily . Many people respond with guilt, fear , or blame when a genetic disorder is diagnosed in the family, or they may overprotect the affected member. Support groups are often good sources of information about Turner syndrome; they can offer helpful suggestions about living with it as well as emotional support.

KEY TERMS

Bicuspid aortic valve —A condition in which the major blood vessel from the heart has only two rather than three components to the valve regulating blood flow.

Coarctation of the aorta —A congenital defect in which severe narrowing or constriction of the aorta obstructs the flow of blood.

Mosaic —A term referring to a genetic situation in which an individual's cells do not have the exact same composition of chromosomes. In Down syndrome, this may mean that some of the individual's cells have a normal 46 chromosomes, while other cells have an abnormal 47 chromosomes.

Ovary —One of the two almond-shaped glands in the female reproductive system responsible for producing eggs and the sex hormones estrogen and progesterone.

Resources

BOOKS

All about Me: Growing Up with Turner Syndrome and Nonverbal Learning Disabilities. Wallington, VT: Maple Leaf Center, 2004.

Roche, Alex F., and Shumei S. Sun. Human Growth: Assessment and Interpretation. Cambridge, UK: Cambridge University Press, 2003.

Turner Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: Icon Health Publications, 2004.

ORGANIZATIONS

Human Growth Foundation. 997 Glen Cove Avenue, Glen Head, NY 11545. Web site: <www.hgfound.org>.

Turner Syndrome Society of the United States. 14450 TC Jester, Houston, TX 77014. Web site: <www.turner-syndrome-us.org>.

Turner Syndrome Support Society (UK). Hardgate, Clydebank, UK. Web site: <http://tss.org.uk>.

WEB SITES

"Turner Syndrome." National Institute of Child Health and Human Development, National Institutes of Health. Available online at <http://turners.nichd.nih.gov/> (accessed November 15, 2004).

Judith Sims, MS L. Fleming Fallon, MD, PhD, DrPH

Turner Syndrome

Definition

Turner syndrome is a chromosomal disorder affecting females wherein one of the two X-chromosomes is defective or completely absent.

Description

Chromosomes are structures in the nucleus of every cell in the human body. Chromosomes contain the genetic information necessary to direct the growth and normal functioning of all cells and systems of the body. A normal individual has a total of 46 chromosomes in each cell, two of which are responsible for determining gender. Normally, females have two X-chromosomes and males have one X and one Y-chromosome.

In Turner syndrome, an error occurring very early in development results in an abnormal number and arrangement of chromosomes. Most commonly, an individual with Turner syndrome will be born with 45 chromosomes in each cell rather than 46. The missing chromosome is an X-chromosome. The affected person is always female.

The prevalence of Turner syndrome is widely reported as being approximately one per 2,000 live female births, although researchers have reported prevalence rates that range from one in 3,125 to one in 5,000 live female births.

About 1% to 2% of all female conceptions have a missing X-chromosome. Of these, the majority (99%) spontaneously abort, usually during the first trimester of pregnancy. With ultrasound being used more frequently, researchers have realized that some pregnancies with a missing X-chromosome that progress into the second trimester are associated with nuchal cysts, severe lymphedema, or hydrops fetalis. These pregnancies are associated with a high frequency of fetal death.

Causes and symptoms

Turner's syndrome is a disorder associated with characteristic defects in the X-chromosome. The most common presentation is a female with a single X-chromosome and an absent X-chromosome. A Greek study from 1999 reported that the intact X-chromosome was as likely to come from the mother as from the father. This means that there is no parental pattern of responsibility for the missing or defective X-chromosome.

Another less common genetic pattern for Turner Syndrome (35%) is a mosaic. A Danish study reported that mosaicism has an effect on malformations that are associated with Turner syndrome. Research reported in 1997 noted that the karyotype can have a significant effect on the growth of children with Turner syndrome.

The exact location of the genes on the X-chromosome involved in Turner syndrome has not been determined as of 2001. At present, evidence exists that there is a locus for stature on the distal portion of the short arm; there are loci for normal ovarian function on both the short and long arms; and there are loci contributing to fetal viability on the long arm of X.

Turner syndrome is characterized by retarded growth that leads to a small stature and frequent infertility. Individuals with Turner syndrome report an increased incidence of fractures in childhood and osteoporotic fractures in adulthood. The incidence of diabetes mellitus (both insulin dependent and noninsulin dependent varieties) has been reported to be increased in Turner syndrome. Ischemic heart disease, stroke and hypertension are also more common.

Growth in children with Turner syndrome is characterized by a slight intrauterine growth retardation, relatively normal growth rates for the first several years of life, a progressive deceleration of growth later in childhood, and the lack of a pubertal growth spurt. Growth patterns of Chinese girls with Turner syndrome parallel those of Caucasians, although their ultimate height is still less than normal.

Contrary to earlier reports, most individuals with Turner syndrome are not mentally retarded. They may have some learning disabilities, particularly with regard to spatial perception, visual-motor coordination, and mathematics. As a result, the nonverbal IQ in Turner syndrome tends to be lower than the verbal IQ.

Cardiovascular malformations are well-recognized congenital anomalies in Turner syndrome. Dilation and dissection of the aorta are reported in approximately half of women with Turner syndrome. Because of the potential consequences of aortic dilation, some experts recommend screening all individuals with Turner syndrome. However, the specific timing for this screening remains controversial in 2001.

Juvenile arthritis, an autoimmune condition, has been recently (1998) associated with Turner syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. Women with Turner syndrome have an elevated prevalence rate of dental caries and such other periodontal conditions as gum disease and plaque.

Normal pubertal development and spontaneous menstrual periods do not occur in the majority of children with Turner' syndrome. It is estimated that 3-8% of girls with a single X-chromosome and 12-21% of females with sex chromosome mosaicism may have normal pubertal development and spontaneous menstrual periods. A few pregnancies have been reported in women with Turner syndrome.

Diagnosis

Turner syndrome is diagnosed on the basis of genetic analysis of chromosomes. This can be done prior to birth. However, the predictive value of amniocentesis in diagnosing Turner syndrome varies from 21-67%. There is no significant relation between the mother's age and risk of Turner's syndrome.

Treatment

Because it is so dangerous, experts suggest screening for aortic dissection, although the specific timing for this screening is controversial. Plastic surgery to correct webbing of the neck should be considered at an early age (before entering school) for girls with Turner syndrome.

Most individuals with Turner syndrome require female hormone therapy to promote development of secondary sexual characteristics and menstruation. The time of beginning therapy varies with individuals. Experts recommend that therapy begin when a woman expresses concern about her onset of puberty.

All women receiving long-term, exogenous female hormone therapy require periodic gynecological examinations, because those with Turner syndrome have an increased risk of developing neoplasms such as gonadoblastoma and dysgerminoma, which arise from their rudimentary streak gonads.

Prognosis

Most women with Turner syndrome can live relatively normal lives. The prognosis for a person with Turner syndrome is dependent on other conditions that may be present. Care must be taken to regularly monitor them for the health problems that are associated with Turner syndrome. For example, heart or kidney defects, hearing loss, or the development of inflammatory bowel disease may significantly impact the quality of life. Without these types of conditions, however, their life expectancy is normal. Support will be necessary to help an adolescent girl cope with body image issues and to help some women accept the fact that they will never be able to have children.

KEY TERMS

Chromosome— A microscopic thread-like structure found within each cell of the body that consists of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the total number of chromosomes or their shape and size (structure) may lead to physical or mental abnormalities.

Mosaic— A term referring to a genetic situation in which an individual's cells do not have the exact same composition of chromosomes. In Down syndrome, this may mean that some of the individual's cells have a normal 46 chromosomes, while other cells have an abnormal 47 chromosomes.

Ovary— The female reproductive organ that produces the reproductive cell (ovum) and female hormones.

Zygote— The cell formed by the uniting of egg and sperm.

Resources

BOOKS

Hall, Judith G. "Chromosomal Clinical Abnormalities." In Nelson Textbook of Pediatrics, edited by Richard E Behrman, et al., 16th ed. Philadelphia: W.B. Saunders, 2000, pp. 325-334.

ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax: (847) 434-8000. 〈http://www.aap.org/visit/contact.htm〉.

Endocrine Society. 4350 East West Highway, Suite 500, Bethesda, MD 20814-4410. (301) 941-0200. Fax: (301) 941-0259. [email protected].

Human Growth Foundation. 997 Glen Cove Ave., Glen Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055. 〈http://www.hgfound.org〉.

Turner Syndrome Society of Canada. 7777 Keele St, Floor 2, Concord, ONT L4K 1Y7. Canada (800) 465-6744 or (416) 660-7766. Fax: (416) 660-7450.

Turner Syndrome Society of England. 2 Mayfield Ave., London, W41PW. UK 44 (0)181-994 7625. Fax: 44 (0)181-995 9075. 〈http://www.exnet.com/staff/sys4/ts.html〉 or 〈http://www.tss.org.uk〉.

OTHER

American Academy of Pediatrics. 〈http://www.aap.org/visit/contact.htm〉.

On-ramp Access. 〈http://www.onr.com/ts-texas/turner.html〉.

Turner Syndrome Support Society(UK). 〈http://www.tss.org.uk/〉.

University of Kansas Medical Center. 〈http://www.kumc.edu/gec/support/turner.html〉.

Turner syndrome

Definition

Turner syndrome is a chromosomal disorder affecting females wherein one of the two X-chromosomes is defective or completely absent.

Description

Chromosomes are structures in the nucleus of every cell in the human body. Chromosomes contain the genetic information necessary to direct the growth and normal functioning of all cells and systems of the body. A normal individual has a total of 46 chromosomes in each cell, two of which are responsible for determining gender. Normally, females have two X chromosomes and males have one X and one Y chromosome.

In Turner syndrome, an error occurring very early in development results in an abnormal number and arrangement of chromosomes. Most commonly, an individual with Turner syndrome will be born with 45 chromosomes in each cell rather than 46. The missing chromosome is an X chromosome. The affected person is always female.

Genetic profile

Turner syndrome is a disorder associated with characteristic defects in the X chromosome. The most common presentation is a female with a single X chromosome and an absent X chromosome. A Greek study from 1999 reported that the intact X chromosome was as likely to come from the mother as from the father. This means that there is no parental pattern of responsibility for the missing or defective X chromosome.

Another less common genetic pattern for Turner syndrome (35%) is a mosaic. A Danish study reported that mosaicism has an effect on malformations that are associated with Turner syndrome. Research reported in 1997 noted that the karyotype can have a significant effect on the growth of children with Turner syndrome.

The exact location of the genes on the X chromosome involved in Turner syndrome has not been determined as of 2001. At present, evidence exists that there is a locus for stature on the distal portion of the short arm; there are loci for normal ovarian function on both the short and long arms; and there are loci contributing to fetal viability on the long arm of X.

Demographics

The prevalence of Turner syndrome is widely reported as being approximately one per 2,000 live female births although researchers have reported prevalence rates that range from one in 3,125 to one in 5,000 live female births.

About 1-2% of all female conceptions have a missing X chromosome. Of these, the majority (99%) spontaneously abort, usually during the first trimester of pregnancy. With ultrasound being used more frequently, researchers have realized that some pregnancies with a missing X chromosome that progress into the second trimester are associated with nuchal cysts, severe lymphedema, or hydrops fetalis . These pregnancies are associated with a high frequency of fetal death.

Signs and symptoms

Turner syndrome is characterized by delayed growth that leads to a small stature and frequent infertility. Individuals with Turner syndrome report an increased incidence of fractures in childhood and osteoporotic fractures in adulthood. The incidence of diabetes mellitus (both insulin dependent and non-insulin dependent varieties) has been reported to be increased in Turner syndrome. Ischemic heart disease, stroke, and hypertension are also more common.

Growth in children with Turner syndrome is characterized by a slight intrauterine growth retardation, relatively normal growth rates for the first several years of life, a progressive deceleration of growth later in childhood, and the lack of a pubertal growth spurt. Growth patterns of Chinese girls with Turner syndrome parallel those of Caucasians, although their ultimate height is still less than normal.

Contrary to earlier reports, most individuals with Turner syndrome are not mentally retarded. They may have some learning disabilities, particularly with regard to spatial perception, visual-motor coordination, and mathematics. As a result, the nonverbal IQ in Turner syndrome tends to be lower than the verbal IQ.

Cardiovascular malformations are well-recognized congenital anomalies in Turner syndrome. Dilation and dissection of the aorta are reported in approximately half of women with Turner syndrome. Because of the potential consequences of aortic dilation, some experts recommend screening all individuals with Turner syndrome. However, the specific timing for this screening remains controversial in 2001.

Juvenile arthritis, an autoimmune condition, has been recently (1998) associated with Turner syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. Women with Turner syndrome have an elevated prevalence rate of dental caries and other periodontal conditions such as gum disease and plaque.

Normal pubertal development and spontaneous menstrual periods do not occur in the majority of children with Turner syndrome. It is estimated that 3-8% of girls with a single X chromosome and 12-21% of females with sex chromosome mosaicism may have normal pubertal development and spontaneous menstrual periods. A few pregnancies have been reported in women with Turner syndrome.

Diagnosis

Turner syndrome is diagnosed on the basis of genetic analysis of chromosomes. This can be done prior to birth. However, the predictive value of amniocentesis in diagnosing Turner syndrome varies from 21-67%. There is no significant relation between mother's age and risk of Turner syndrome.

Treatment and management

Because it is so dangerous, experts suggest screening for aortic dissection, although the specific timing for this screening is controversial. Plastic surgery to correct webbing of the neck should be considered at an early age (before entering school) for girls with Turner syndrome.

Most individuals with Turner syndrome require female hormone therapy to promote development of secondary sexual characteristics and menstruation. The time of beginning therapy varies with individuals. Experts recommend that therapy begin when a woman expresses concern about her onset of puberty.

All women receiving long term, exogenous female hormone therapy require periodic gynecological examinations because those with Turner syndrome have an increased risk of developing neoplasms such as gonadoblastoma and dysgerminoma, which arise from their rudimentary streak gonads.

Prognosis

Most women with Turner syndrome can live relatively normal lives. The prognosis for people with Turner syndrome is dependent on other conditions that may be present. Care must be taken to regularly monitor them for the health problems that are associated with Turner syndrome. For example, heart or kidney defects, hearing loss, or the development of inflammatory bowel disease may significantly impact the quality of life. Without these types of conditions, however, their life expectancy is normal. Support will be necessary to help an adolescent girl cope with body image issues and to help some women accept the fact that they will never be able to have children.

Resources

BOOKS

Hall, Judith G. "Chromosomal Clinical Abnormalities." In Nelson Textbook of Pediatrics, edited by Richard E. Behrman, et al. 16th ed. Philadelphia: W.B. Saunders, 2000, pp. 325-334.

Jones, K.L. "XO Syndrome." In Smith's Recognizable Patterns of Human Malformation. Edited by Kenneth L. Jones and Judy Fletcher. 5th ed. Philadelphia: W.B. Saunders, 1997, pp. 81-87.

Plumridge, D. Good Things Come in Small Packages: The Whys and Hows of Turner Syndrome. Portland, OR: University of Oregon Health Sciences Center, 1987.

Reiser, P.A., and L.E. Underwood. Turner Syndrome: A Guide for Families. Wayzata, MN: Turner Syndrome Society, 1992.

PERIODICALS

Gravholt, C.H., et al. "Morbidity in Turner Syndrome." Journal of Clinical Epidemiology 51, no. 2 (February 1998): 147-158.

Gravholt, C.H., et al. "Prenatal and Postnatal Prevalence of Turner's Syndrome: A Registry Study." British Medical Journal 312, no. 7022 (January 6, 1996): 16-21.

Zinn, A.R., D.C. Page, and E.M. Fisher. "Turner Syndrome: The Case of the Missing Sex Chromosome." Trends in Genetics 9 (1993): 90-93.

ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax: (847) 434-8000. <http://www.aap.org/visit/contact.htm>.

Endocrine Society. 4350 East West Highway, Suite 500, Bethesda, MD 20814-4410. (301) 941-0200. Fax: (301) 941-0259. [email protected].

Human Growth Foundation. 997 Glen Cove Ave., Glen Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055. <http://[email protected]>.

MAGIC Foundation for Children's Growth. 1327 N. Harlem Ave., Oak Park, IL 60302. (708) 383-0808 or (800) 362-4423. Fax: (708) 383-0899. [email protected]. <http://www.magicfoundation.org/ghd.html>.

Turner Syndrome Society of Canada. 7777 Keele St, Floor 2, Concord, ONT L4K 1Y7. Canada (800) 465-6744 or (416) 660-7766. Fax: (416) 660-7450.

Turner Syndrome Society of England. 2 Mayfield Ave., London, W41PW. UK 44 (0)181-994 7625. Fax: 44 (0)181-995 9075. <http://www.exnet.com/staff/sys4/ts.html> or <http://www.tss.org.uk>.

Turner Syndrome Society of the United States. 14450 T. C. Jester, Suite 260, Houston, TX 77014. (800) 365-9944 or (832) 249-9988. Fax: (832) 249-9987. [email protected]. <http://www.turner-syndrome-us.org>.

WEBSITES

American Academy of Pediatrics. <http://www.aap.org/visit/contact.htm>.

On-ramp Access. <http://www.onr.com/ts-texas/turner.html>.

Turner Syndrome Support Society (UK). <http://www.tss.org.uk/>.

University of Kansas Medical Center. <http://www.kumc.edu/gec/support/turner.html>.

L. Fleming Fallon, Jr., MD, PhD, DrPH

Turner syndrome

Definition

Turner syndrome is a chromosomal disorder affecting females wherein one of the two X chromosomes is defective or completely absent.

Description

Chromosomes are structures in the nucleus of every cell in the human body. Chromosomes contain the genetic information necessary to direct the growth and normal functioning of all cells and systems of the body. A normal individual has a total of 46 chromosomes in each cell, two of which are responsible for determining gender. Normally, females have two X chromosomes and males have one X and one Y chromosome .

In Turner syndrome, an error occurring very early in development results in an abnormal number and arrangement of chromosomes. Most commonly, an individual with Turner syndrome will be born with 45 chromosomes in each cell rather than 46. The missing chromosome is an X chromosome. The affected person is always female.

Genetic profile

Turner syndrome is a disorder associated with characteristic defects in the X chromosome. The most common presentation is a female with a single X chromosome and an absent X chromosome. A Greek study from 1999 reported that the intact X chromosome was as likely to come from the mother as from the father. This means that there is no parental pattern of responsibility for the missing or defective X chromosome.

Another less common genetic pattern for Turner syndrome (35%) is a mosaic. A Danish study reported that mosaicism has an effect on malformations that are associated with Turner syndrome. Research reported in 1997 noted that the karyotype can have a significant effect on the growth of children with Turner syndrome.

The exact location of the genes on the X chromosome involved in Turner syndrome has not been determined as of 2001. At present, evidence exists that there is a locus for stature on the distal portion of the short arm; there are loci for normal ovarian function on both the short and long arms; and there are loci contributing to fetal viability on the long arm of X.

Demographics

The prevalence of Turner syndrome is widely reported as being approximately one per 2,000 live female births although researchers have reported prevalence rates that range from one in 3,125 to one in 5,000 live female births.

About 1–2% of all female conceptions have a missing X chromosome. Of these, the majority (99%) spontaneously abort, usually during the first trimester of pregnancy. With ultrasound being used more frequently, researchers have realized that some pregnancies with a missing X chromosome that progress into the second trimester are associated with nuchal cysts, severe lymphedema, or hydrops fetalis . These pregnancies are associated with a high frequency of fetal death.

Signs and symptoms

Turner syndrome is characterized by delayed growth that leads to a small stature and frequent infertility. Individuals with Turner syndrome report an increased incidence of fractures in childhood and osteoporotic fractures in adulthood. The incidence of diabetes mellitus (both insulin dependent and non-insulin dependent varieties) has been reported to be increased in Turner syndrome. Ischemic heart disease, stroke, and hypertension are also more common.

Growth in children with Turner syndrome is characterized by a slight intrauterine growth retardation, relatively normal growth rates for the first several years of life, a progressive deceleration of growth later in childhood, and the lack of a pubertal growth spurt. Growth patterns of Chinese girls with Turner syndrome parallel those of Caucasians, although their ultimate height is still less than normal.

Contrary to earlier reports, most individuals with Turner syndrome are not mentally retarded. They may have some learning disabilities, particularly with regard to spatial perception, visual-motor coordination, and mathematics. As a result, the nonverbal IQ in Turner syndrome tends to be lower than the verbal IQ.

Cardiovascular malformations are well-recognized congenital anomalies in Turner syndrome. Dilation and dissection of the aorta are reported in approximately half of women with Turner syndrome. Because of the potential consequences of aortic dilation, some experts recommend screening all individuals with Turner syndrome. However, the specific timing for this screening remains controversial in 2001.

Juvenile arthritis, an autoimmune condition, has been recently (1998) associated with Turner syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. Women with Turner syndrome have an elevated prevalence rate of dental caries and other periodontal conditions such as gum disease and plaque.

Normal pubertal development and spontaneous menstrual periods do not occur in the majority of children with Turner syndrome. It is estimated that 3-8% of girls with a single X chromosome and 12-21% of females with sex chromosome mosaicism may have normal pubertal development and spontaneous menstrual periods. A few pregnancies have been reported in women with Turner syndrome.

Diagnosis

Turner syndrome is diagnosed on the basis of genetic analysis of chromosomes. This can be done prior to birth. However, the predictive value of amniocentesis in diagnosing Turner syndrome varies from 21-67%. There is no significant relation between mother's age and risk of Turner syndrome.

Treatment and management

Because it is so dangerous, experts suggest screening for aortic dissection, although the specific timing for this screening is controversial. Plastic surgery to correct webbing of the neck should be considered at an early age (before entering school) for girls with Turner syndrome.

Most individuals with Turner syndrome require female hormone therapy to promote development of secondary sexual characteristics and menstruation. The time of beginning therapy varies with individuals. Experts recommend that therapy begin when a woman expresses concern about her onset of puberty.

All women receiving long term, exogenous female hormone therapy require periodic gynecological examinations because those with Turner syndrome have an increased risk of developing neoplasms such as gonadoblastoma and dysgerminoma, which arise from their rudimentary streak gonads.

Prognosis

Most women with Turner syndrome can live relatively normal lives. The prognosis for people with Turner syndrome is dependent on other conditions that may be present. Care must be taken to regularly monitor them for the health problems that are associated with Turner syndrome. For example, heart or kidney defects, hearing loss, or the development of inflammatory bowel disease may significantly impact the quality of life. Without these types of conditions, however, their life expectancy is normal. Support will be necessary to help an adolescent girl cope with body image issues and to help some women accept the fact that they will never be able to have children.

Resources

BOOKS

Hall, Judith G. "Chromosomal Clinical Abnormalities." Nelson Textbook of Pediatrics, edited by Richard E Behrman, et al. 16th ed. Philadelphia: W.B. Saunders, 2000, pp. 325-334.

Jones, K.L. "XO Syndrome." Smith's Recognizable Patterns of Human Malformation, edited by Kenneth L. Jones and Judy Fletcher. 5th ed. Philadelphia: W.B. Saunders, 1997, pp. 81-87.

Plumridge, D. Good Things Come in Small Packages: The Whys and Hows of Turner Syndrome. Portland, OR: University of Oregon Health Sciences Center, 1987.

Reiser, P.A., and L.E. Underwood. Turner Syndrome: A Guide for Families. Wayzata MN: Turner Syndrome Society; 1992.

PERIODICALS

Gravholt, C.H., et al. "Morbidity in Turner Syndrome." Journal of Clinical Epidemiology 51, no. 2 (February 1998): 147-158.

Gravholt, C.H., et al. "Prenatal and Postnatal Prevalence of Turner's Syndrome: A Registry Study." British Medical Journal 312, no. 7022 (January 6, 1996): 16-21.

Zinn, A.R., D.C. Page, and E.M. Fisher. "Turner Syndrome: The Case of the Missing Sex Chromosome." Trends in Genetics 9 (1993): 90-93.

ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax: (847) 434-8000. <http://www.aap.org/visit/contact.htm>.

Endocrine Society. 4350 East West Highway, Suite 500, Bethesda, MD 20814-4410. (301) 941-0200. Fax: (301) 941-0259. [email protected].

Human Growth Foundation. 997 Glen Cove Ave., Glen Head, NY 11545. (800) 451-6434. Fax: (516) 671-4055. <http://[email protected]>.

MAGIC Foundation for Children's Growth. 1327 N. Harlem Ave., Oak Park, IL 60302. (708) 383-0808 or (800) 362-4423. Fax: (708) 383-0899. [email protected]. <http://www.magicfoundation.org/ghd.html>.

Turner Syndrome Society of Canada. 7777 Keele St, Floor 2, Concord, ONT L4K 1Y7. Canada (800) 465-6744 or (416) 660-7766. Fax: (416) 660-7450.

Turner Syndrome Society of England. 2 Mayfield Ave., London, W41PW. UK 44 (0)181-994 7625. Fax: 44 (0)181-995 9075. <http://www.exnet.com/staff/sys4/ts.html> or <http://www.tss.org.uk>.

Turner Syndrome Society of the United States. 14450 T. C. Jester, Suite 260, Houston, TX 77014. (800) 365-9944 or (832) 249-9988. Fax: (832) 249-9987. [email protected]. <http://www.turner-syndrome-us.org>.

WEBSITES

American Academy of Pediatrics. <http://www.aap.org/visit/contact.htm>.

On-ramp Access. <http://www.onr.com/ts-texas/turner.html>.

Turner Syndrome Support Society (UK). <http://www.tss.org.uk/>.

University of Kansas Medical Center. <http://www.kumc.edu/gec/support/turner.html>.

L. Fleming Fallon, Jr., MD, PhD, DrPH

Turner Syndrome

Genetic defects

Clinical manifestations of Turner syndrome

Loss of gene function and developmental consequences

Resources

Turner syndrome (also referred to as gonadal dys-genesis) is a rare genetic disorder that involves several chromosomal abnormalities (monosomy X chromosome is the most common one affected), which only affects females. In Turner syndrome, sexual characteristics are found to be underdeveloped within females. Approximately one in 2,000 to 5,000 females in the general population are affected with Turner syndrome, and about one out of every 2,500 live female births. This is a large percentage considering that about 99% of pregnancies with fetuses affected with Turner syndrome spontaneously abort, usually during the first trimester of pregnancy. It is also estimated that 10% of all spontaneously aborted fetuses result from Turner syndrome.

Genetic defects

Turner syndrome was named after American endocrinologist Henry Turner, who described the disorder in 1938. It was also described by European doctors, which causes it to be also called by such names as Ullrich-Turner syndrome or BonnevieUlrich-Turner syndrome. Later, Turner syndrome was found to be due to a loss of genetic material in one of the two X-chromosomes. There are several ways in which Turner syndrome arises. Females have two X-chromosomes, while males have an X-chromosome and a Y-chromosome. While a Y-chromosome contains genes required for development of testicles in males, both X-chromosomes are required for normal ovarian development in females. The majority of Turner syndrome cases are caused by a sporadic event during a specific stage of cellular division, where an X-chromosome is lost. Normally, when sex cells divide, an equal amount of genetic material is divided into each cell. During fertilization of the egg, if the sex cell void of the X-chromosome is fertilized by a sex cell that is missing the other X-chromosome, the result is only one sex chromosome. If the fetus survives, the baby will be born with Turner syndrome. A fertilized egg with only one Y-chromosome is incompatible with life.

Turner syndrome can also result from the loss of a single X-chromosome after fertilization, sometime during embryonic development. This particular condition is referred to as mosaicism, with clinical manifestations being proportional to the percentage of cells missing the X-chromosome. Finally, Turner syndrome can result due to a defective X-chromosome such as large deletion. The clinical consequences vary depending on the nature of the structural abnormality of the X-chromosome. In the case X-chromosome deletions, where affected individuals are fertile, there is potential for a recurrence risk in pregnancies from an affected female. Otherwise, there is typically little recurrence risk (if any) in subsequent pregnancies or in individuals with Turner syndrome since the majority of these individuals are infertile.

Clinical manifestations of Turner syndrome

There are a broad spectrum of clinical manifestations associated with Turner syndrome that can involve anything from major heart defects to minor defects in tissue development. Some affected individuals only manifest a few clinical features, while others have many abnormalities consistent with the disorder. The majority of individuals with Turner syndrome have short stature and loss of ovarian function. Other disorders include learning difficulties, skeletal abnormalities (e.g., webbed neck, low posterior hair line), lymphedema (swelling of a part of the body (such as feet or hands) due to an obstruction or deficiency of the lymphatic drainage system), heart and kidney abnormalities, infertility, obesity, formation of keloids (thick scars), and thyroid gland dysfunction (hypothyroidism).

Other common characteristics include: upturned nails, drooping eyelids, small lower jaw, loss of hearing, pigmented moles, broad chest with nipples that are abnormally spaced apart, absence of a menstrual period, and ears positioned abnormally low with respect to other facial features.

Loss of gene function and developmental consequences

Short stature is usually present in females with Turner syndrome. This is partially due to a loss of the SHOX gene, which encodes a protein important for long bone growth. The height in adults with Turner syndrome ranges from 4 ft 8 in to 4 ft 9 in (143 to 145 cm). Treatment using growth hormones during early childhood development can increase growth by a few inches in some cases. The loss of the X-chromosome genes may also be related to the intrauterine growth retardation, a gradual decline in growth rate during childhood, and the absence of a pubertal growth spurt. Females with Turner syndrome have abnormal body proportions characterized by markedly shortened lower extremities.

Lost X-chromosome genes that are involved in the regulation of ovarian development and function results in a failure of individuals with Turner syndrome to enter into puberty at a normal age. Although 10% of females with Turner syndrome will go through puberty spontaneously, most will require hormone therapy for development of secondary sexual characteristics and menstruation. Without hormonal intervention, most teenagers that undergo partial breast development and menstruate spontaneously will eventually cease further development and menstruation. A few pregnancies have been reported and most likely occur prior to ovarian failure. The time of initiation of therapy varies with each female but usually begins no later than 15 years of age. Various estrogenic and progestational agents and schedules have been used as hormone therapy to maintain their secondary sexual development and prevent osteoporosis (bone degradation) later in life. Although most women with Turner syndrome do not have functional ovaries, pregnancy may be possible through in vitro fertilization (assisted reproductive technology).

Renal abnormalities occur in one-third to one-fourth of females with Turner syndrome. The most common abnormality is a horseshoe kidney. Cardiac abnormalities are also common, with the coarctation of the aorta being the most common defect. This is a condition that results from a severe constriction a major blood vessel in the heart, can be treated with surgery, and occurs in 5 to 10% of affected children. Turner syndrome females generally have normal intelligence, however, most may exhibit learning disabilities, especially with regard to spatial perception, visual-motor coordination, and mathematics. As a result, the nonverbal IQ (intelligence quotient) in Turner syndrome tends to be lower, with a relatively normal verbal IQ. Females with Turner syndrome may also be socially immature for their age and may need support in developing independence and social relationships.

See also Gene mutation; Genetic engineering; Genetics; Skeletal system.

Resources

BOOKS

Nussbaum, R.L., Roderick R. McInnes and Huntington F.
Willard. Genetics in Medicine. Philadelphia, PA:
Saunders, 2001.

Rieser, Patricia A. Turner Syndrome: A Guide for Families.
Houston, TX: Turner Syndrome Society, 2003.

Rimoin, D.L. Emery and Rimoin’s Principles and Practice of
Medical Genetics. London, UK; New York: Churchill Livingstone, 2002.

OTHER

Turner Syndrome Society, “Turner Syndrome Society of the
United States.” <http://www.turner-syndrome-us.org/> (accessed December 3, 2006).

Bryan Cobb, Ph.D.